Summary of Work A) We have analyzed the histopathology of the first 100 cases entered onto the NSCLC protocol (83-15). These studies indicate a continuation of a trend noticed earlier, namely a dramatic absolute and relative decrease in the incidence of squamous cell carcinoma, and an absolute and relative increase in the incidence of adenocarcinoma, especially bronchioloalveolar carcinoma (BAC). B) We have developed methods and media for the selective growth of lung and colorectal carcinomas. With these techniques, our successful culture rates (per adequate tumor containing sample) are as follows: Small cell lung cancer (SCLC) 46%; non-SCLC (NSCLC) 23%; colorectal carcinoma 35%. C) Currently, 48 NSCLC lines have been established and partly or completely characterized. They include several unique lines including mucoepidermoid, BAC and carcinoids. The BAC lines include several releasing large amounts of fully processed surfactant, and are being explored for use in the respiratory distress syndrome of neonates. D) About 12% of NSCLC tumors express neuroendocrine properties similar to SCLC. We have established 5 lines from these tumors. Their in vitro chemosensitivity profiles are similar to those of SCLC cell lines and different from the relatively resistant profiles of NSCLC lines. These data suggest that a subset of NSCLC tumors (13000 cases/year) may be relatively chemosensitive. We have modified a semiautomated (MTT) dye assay for in vitro chemosensitivity testing. The test is highly reproducible. Extensive testing of lung and colorectal cell lines suggest that in vitro testing may have relevance as a drug prescreen as well as for individualized selection of chemotherapy.